The existence of the blood-brain barrier (BBB) makes the treatment of brain diseases significantly challenging. Delivery of drug-loaded carriers (nanoparticles) across BBB through receptor-mediated transcytosis (RMT) is a noninvasive and effective strategy to overcome the challenge. During RMT, the nanoparticles actively interact with the membrane and the membrane profle involves extreme deformations during particle internalization and expulsion. Recently we have developed a stochastic model to study the endocytosis and exocytosis during nanoparticles across BBB. The model is based on the combination of a stochastic particle binding model with a membrane model, and accounts for both the clathrin-mediated endocytosis at the blood side and the actin-mediated exocytosis at the brain side. In this talk, through our model and simulations we will present the systematic investigations of the effects from a variety of geometrical and biochamical factors on the overall RMT effeciency. Specifically, we will discuss the effects of particle size, particle shape, ligand density, ligand-receptor binding affinity, chathrin, actin and membrane bending rigidities. The simulation results are consistent with the corresponding experiments. The model is able to provide mechanistic insights into RMT, and represents a powerful platform for aiding the rational design of drug carriers for intra/transcellular drug delivery.

Biographical Sketch:

Dr. Jin Liu is currently an Associate Professor in the School of Mechanical and Materials Engineering at Washington State Univeristy. He received his B.S. degree in Mechanical Engineering from University of Science and Technology of China in 2001. He received his M.S. and Ph.D. degrees in Mechanical Engineering from University of Michigan, Ann Arbor in 2003 and from Johns Hopkins University in 2008, respectively. Then he spent three years in the Department of Bioengineering at University of Pennsylvania as a postdoctoral associate. His current research interests mainly focus on mesoscale modeling of targeted drug delivery, simulations of protein structures, computational fluid dynamics (CFD), and multi-scale modeling and their applications in engineering and biomedical processes.